1. Field of the Invention
This invention relates to a method for the extremely effective in vitro immunization of lymphocytes for the production of antibody specific to the antigen, as well as a method for the assay of immunization stimulating activity by applying a cell culture system.
2. Description of the Prior Art
Since Kohler and Milstein established, in 1975, a method for generating mouse hybridoma cell lines producing monoclonal antibodies in vitro (Nature 1975, 256, 495-497), innumerable monoclonal antibodies of mouse origin directed to various antigens have been developed and many of them are currently being employed for the in vitro diagnostic use such as serodiagnosis. Although human monoclonal antibodies can also be produced by applying the method of Kohler and Milstein and these antibodies of mouse and human origins are anticipated for the therapeutic use, no monoclonal antibody has ever employed in practical therapy.
It is a generally accepted concept that monoclonal antibodies of human origin are preferable for administration to humans than those of mouse origin. However, applications of human monoclonal antibodies to the clinical use have been hampered thus far partly due to the lack of effective methods for providing human lymphocytes immunized with the requested antigens, which are indispensable for the generation of hybridomas in concern, and partly due to the ethical reason that immunizations with favorable antigens in humans are not possible. In this context, extensive efforts are being made to establish efficient in vitro immunization methods to overcome the difficulties (J. Immunol. 1985, 135, 3831-3838; Human Hybridoma and Monoclonal Antibody, Plenum Press, 1985, pp. 71-91).